The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
Criteria Specification: CSpec Registry PDF

Variant: NM_000277.2(PAH):c.464G>C (p.Arg155Pro)

CA229561

102687 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: a532eae1-862f-4d90-b69e-5e590a9f7512

HGVS expressions

NM_000277.2:c.464G>C
NM_000277.2(PAH):c.464G>C (p.Arg155Pro)
NC_000012.12:g.102866641C>G
CM000674.2:g.102866641C>G
NC_000012.11:g.103260419C>G
CM000674.1:g.103260419C>G
NC_000012.10:g.101784549C>G
NG_008690.1:g.55962G>C
NG_008690.2:g.96770G>C
NM_000277.1:c.464G>C
NM_001354304.1:c.464G>C
NM_000277.3:c.464G>C
ENST00000307000.7:c.449G>C
ENST00000549111.5:n.560G>C
ENST00000551988.5:n.530+10821G>C
ENST00000553106.5:c.464G>C

Likely Pathogenic

Met criteria codes 4
PM3 PM2 PP3 PP4_Moderate

Expert Panel

Evidence Links 1

Evidence submitted by expert panel
PAH VCEP
PAH-specific ACMG/AMP criteria applied: PM2: absent from ExAC, gnomAD, 1000G, ESP. PAGE MAF=0.00066; PP3: Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.967; PP4_Moderate: Detected in a patient with classic PKU. Cofactor deficiency excluded. (PMID:10679941); PM3: Detected in trans with R408W (P) (PMID:10679941). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PP4_Moderate, PM3).
Met criteria codes
PM3
Detected in trans with R408W (P)

PM2
absent from ExAC, gnomAD, 1000G, ESP. PAGE MAF=0.00066
PP3
Deleterious effect predicted in SIFT, Polyphen-2, MutationTaster. REVEL=0.967
PP4_Moderate
Detected in a patient with classic PKU. Cofactor deficiency excluded.

Approved on: 2018-08-10
Published on: 2019-04-06
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